Reduction of the reinforcing effectiveness of cocaine by continuous d-amphetamine treatment in rats: importance of active self-administration during treatment period View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-03

AUTHORS

Benjamin A. Zimmer, Keri A. Chiodo, David C. S. Roberts

ABSTRACT

RATIONALE: Continuous administration of D-amphetamine has shown promise as a treatment for psychostimulant addiction. In rodent studies, constant infusion of D-amphetamine (5 mg/kg/day) has been shown to reduce cocaine-reinforced responding in the dose range of 0.19-0.75 mg/kg/inf. OBJECTIVES: The present study tested whether these effects were a reflection of pharmacological interactions between D-amphetamine and cocaine or if they resulted from associative learning mechanisms METHODS: After stable progressive ratio (PR) baselines were established, rats were implanted with subcutaneous osmotic minipumps filled with either D-amphetamine (5 mg/kg/day-groups 1 and 2) or saline (group 3). During the treatment period, groups 1 and 3 self-administered cocaine at a dose that was previously shown to produce the most robust effects in combination with D-amphetamine treatment (0.19 mg/kg/inf), while group 2 received passive cocaine infusions. RESULTS: In replication of previous studies, D-amphetamine treatment resulted in a significant (35 %) decrease in breakpoints relative to saline controls. By contrast, no reductions in breakpoints were observed in animals that received passive cocaine infusions during the treatment period (group 2). CONCLUSIONS: Active self-administration of cocaine during the treatment period appears to be an important factor in reducing cocaine-reinforced breakpoints. These findings suggest learning mechanisms are involved in the therapeutic effects of continuous D-amphetamine, and pharmacological interaction mechanisms such as cross-tolerance cannot completely account for the observed decreases in cocaine seeking. More... »

PAGES

949-954

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00213-013-3305-4

DOI

http://dx.doi.org/10.1007/s00213-013-3305-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051167519

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24146137


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